國家衛生研究院 NHRI:Item 3990099045/7531
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    题名: Profiles of GABA-A receptor subtypes in human alcoholic brain
    作者: Dodd, P;Kuo, SW
    贡献者: Center for Neuropsychiatric Research
    摘要: Purpose :PET imaging of GABAA receptors uses [11C]flumazenil and [11C] Ro15-4513 as tracers. Flumazenil binds to all sites, Ro15-4513 selects α5-containing receptors. Alcoholics show reduced [11C]Ro15-4513 PET signals in hippocampus and accumbens. We determined tracer-binding parameters in autopsy brain. Methods: We used membrane binding to assayradioligandsand modulatorsin five brain regions from alcoholics and matched controls (n = 6). Data were analysed by non-linear curve-fitting. Results: [14C]Flunitrazepam affinity was invariant, [14C]flumazenil affinity varied regionally, and [14C]Ro15-4513 affinity varied both regionally and between groups. [14C]Flunitrazepam and [14C]flumazenil receptor densitieswerehigher in several brain regions of alcoholics,whereas [14C]Ro15-4513 density was not. Zolpidem affinity in modulating [14C]Ro15-4513 and [14C] flumazenil binding was lower in hippocampus and caudate. Regional differences in Hill slope (nH), notably in occipital cortex, precluded a one-site model. Zolpidem modulation of [14C]flumazenil binding resolved into 2 sites in four regions. Affinity waslower in occipital cortex (52 ± 1 ?M) than in other regions (range 9–12 ?M), P< 0.01, butinvariant across alcoholics and controls. Binding capacities variedregionally but not between case-groups. Zolpidem modulation of [14C]Ro15-4513 bindingresolved into 2 sites in all areas. In controls, the proportion of binding to the high-affinity site was significantly lower in caudate (29%) than in any other region (49–53%); in alcoholics, the fraction differed between hippocampus (27%) and occipital cortex (71%). Regional profiles of binding capacity differed significantly between alcoholics and controls. Conclusions: These data reflectlocal variations in α1 and α5 GABAA subunit expression in alcohol misuse.
    日期: 2013-09
    關聯: Alcohol and Alcoholism. 2013 Sep;48(Suppl. 1):25-26.
    Link to: http://dx.doi.org/10.1093/alcalc/agt103
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0735-0414&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000323348200112
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